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Transcript
The wonderful duplicating
“machine”
A briefe history of the cell cycle
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
QuickTime™ and a
Sorenson Video decompressor
are needed to see this picture.
QuickTime™ and a
Video decompressor
are needed to see this picture.
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
Fluorescent Activated Cell Scan/Sorter
(FACS)
A typical FACS analysis
Methods for cell synchronisation
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase ()
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
Cell fusion experiment
Johnson and Rao 1971
G1
M
M
S
M
M
G2
M
M
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
Maturation promoting factor
cytostatic factor
Discovery of MPF
Masui and Markert 1971
Oscillations of MPF
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
Model organisms I - Budding yeast
(S.cerevisiae)
L. Hartwell
Model organisms II - Fission yeast (S.pombe)
P. Nurse
Generation of temperature sensitive budding
yeast mutants
Generation of temperature sensitive budding
yeast mutants
Analysis of ts cell cycle mutants
G1
S
M
M
M
M
Identification of cell cycle ts mutants
Some ts mutants which became famous
The two models of cell cycle regulation
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
• 18xx Interphase-Mitosis (Flemming)
• 1951 Discovery of a distinct S-phase (Howard and Pelc)
• 1970 Cell fusion experiments (Rao and Johnson)
• 1971 Discovery of MPF (Masui and Markert)
• 197x Yeast cdc mutants (Nurse, Hartwell etc.)
• 1983 Discovery of the first cyclins (Hunt)
• 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)
Oscillations of mitotic cyclins are required for
MPF activity
Regulation of mitotic cyclin levels in cycling
cells
Cdc2/28 (=cdk1) is regulated by:
1. Binding of a cyclin
2. Inhibitory phosphorylation
3. Activating phosophorylation
4. Binding of CKI
5. Cellular localization
QuickTime™ and a
Animation decompressor
are needed to see this picture.